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Consequences of a defective switch in cutaneous squamous cell carcinoma

a cutaneous squamous cell carcinoma and defective switch technology, applied in the field of biochemistry, can solve problems such as poor patient survival rates

Active Publication Date: 2019-10-31
AGENCY FOR SCI TECH & RES
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The present invention relates to methods for treating carcinoma by administering specific oligonucleotides that target certain proteins involved in carcinoma development. The methods may involve using oligonucleotides that reduce the expression of follistatin-related protein 1 (FSTL1), Protein diaphanous homolog 1 (DIAPH1), laminin subunit gamma-2 (LAMC2), or urokinase-type plasminogen activator (PLAU) or their combination. The methods may also involve detecting the presence or absence of miR-198 or the target proteins in a sample and comparing the detected levels with a control sample. The invention also includes the use of expression inhibitors, such as siRNA or shRNA, to further target the expression of the proteins. The technical effect of the invention is to provide effective methods for treating carcinoma by targeting specific proteins involved in carcinoma development.

Problems solved by technology

Aggressive disease progression with high rates of metastasis contributes to poor patient survival rates.

Method used

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  • Consequences of a defective switch in cutaneous squamous cell carcinoma
  • Consequences of a defective switch in cutaneous squamous cell carcinoma
  • Consequences of a defective switch in cutaneous squamous cell carcinoma

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Embodiment Construction

[0036]Carcinomas, for example squamous cell carcinomas (SCC), result from the uncontrolled growth of squamous cells, a subtype of epithelial cell. For example, Head and neck squamous cell carcinomas (HNSCC) develop from mucosal linings of the upper aero-digestive tract, mainly in the nasal cavity, paranasal sinuses, nasopharynx, larynx, trachea, oropharynx and oral cavity.

[0037]The molecular switch disclosed herein is based on the concept that the status of a cell can have an impact, not only on the expression level of a specific gene, but also on what product is expressed by said gene. By way of an explanation, in on example the gene FSTL1 can produce either the pro-migratory FSTL1 protein, or the anti-migratory miR-198, depending on the state of the cell. It is shown, for example, the carcinoma cells have an increased level of FSTL1 protein, which, in itself is, understood to result in the pro-migratory behaviour of carcinoma cells. Carcinoma-free cells, on the contrary, are under...

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Abstract

The present invention refers to a method of treating a carcinoma by administration of one or more of an oligonucleotide comprising the sequence of miR-198 (SEQ ID NO: 1) or a functional part thereof, or an oligonucleotide which reduces expression of Follistatin-related protein 1 (FSTL1), Protein diaphanous homolog 1 (DIAPH1), Laminin subunit gamma-2 (LAMC2) or Urokinase-type plasminogen activator (PLAU). Preferably, the at least one or more oligonucleotides directed against FSTL1, DIAPH1, LAMC2 or PLAU is a shRNA or siRNA. Also provided is a method of determining the presence of carcinoma in a subject, comprising detecting and comparing the presence of miR-198 and / or at least one of FSTL1, DIAPH1, LAMC2 or PLAU, miR-181a, epidermal growth factor (EGF), and epidermal growth factor receptor (EGFR), and comparing the detected levels with that in a control sample.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application claims the benefit of priority of Singapore provisional application no. 10201604845W, filed 14 Jun. 2016, the contents of it being hereby incorporated by reference in its entirety for all purposes.FIELD OF THE INVENTION[0002]The present invention generally relates to the field of biochemistry. In particular, the present invention relates to mi-RNAs, anti-miRNAs and polypeptides, which can be used for the treatment of carcinomas.BACKGROUND OF THE INVENTION[0003]Carcinomas, for example squamous cell carcinomas (SCC), result from the uncontrolled growth of squamous cells, a subtype of epithelial cell. Another example, head and neck squamous cell carcinoma (HNSCC) develops from mucosal linings of the upper aero-digestive tract, mainly in the nasal cavity, paranasal sinuses, nasopharynx, larynx, trachea, oropharynx and oral cavity. Head and neck squamous cell carcinoma (HNSCC) is the sixth highest cancer by incidence worldwide...

Claims

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Application Information

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IPC IPC(8): C12N15/113A61P35/00A61K31/713A61P35/04
CPCC12N2310/531C12N2310/14C12N2320/31A61P35/04C12N15/1137C12N15/113A61K31/713C12N2320/35C12N2310/122A61P35/00C12N2310/141A61K31/7088C12Q1/6886G01N33/5308G01N33/57407G01N33/57415G01N33/57423G01N33/57449G01N2800/52C12Q2600/158C12Q2600/178
Inventor SAMPATH, PRABHAGOPINATH, SUNDARAMQUAH, SHAN
Owner AGENCY FOR SCI TECH & RES
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